Drug delivery device

ABSTRACT

The present disclosure relates to a drug delivery device, comprising a shell adapted to contain one of a plurality of medicament containers prefilled with different deliverable volumes of a medicament. The shell is transparent at least in an area adapted to contain the medicament container, and a label adapted to be arranged on the shell. The label comprises a foil having a first surface and a second surface, which is adapted to be connected to the shell. At least one cutout or transparent area is arranged in the foil adapted to be placed on the shell such that a medicament container arrangeable or arranged within the shell is visible through the cutout or transparent area. The cutout or transparent area exhibits a size adapted to allow inspection of the deliverable volume of medicament within the medicament container when the label is applied to the shell.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a divisional of U.S. patent application Ser.No. 16/317,008, filed Jan. 10, 2019, which is the national stage entryof International Patent Application No. PCT/EP2017/065895, filed on Jun.27, 2017, and claims priority to Application No. EP 16179240.3, filed onJul. 13, 2016, the disclosures of which are incorporated herein byreference.

TECHNICAL FIELD

The disclosure generally relates to a label for a drug delivery device,a drug delivery device having such a label, a kit for assembling a drugdelivery device, and a method of assembling a drug delivery device.

BACKGROUND

Drug delivery devices such as auto-injectors typically allow forvisually inspecting the deliverable volume of drug, e.g. through awindow provided in an outer shell of the drug delivery device.

SUMMARY

According to the present disclosure, a drug delivery device comprises:

-   -   a shell adapted to contain one of a plurality of medicament        containers prefilled with different deliverable volumes of a        medicament, wherein the shell is transparent at least in an area        adapted to contain the medicament container, and    -   a label adapted to be arranged on the shell, wherein the label        comprises a foil having a first surface and a second surface        which is adapted to be connected to the shell, wherein at least        one cutout or transparent area is arranged in the foil adapted        to be placed on the shell such that a medicament container        arrangeable or arranged within the shell is visible through the        cutout or transparent area, wherein the cutout or transparent        area exhibits a size adapted to allow inspection of the        deliverable volume of medicament, e.g. the complete deliverable        volume or a part thereof, within the medicament container when        the label is applied to the shell.

Selecting a label with a cutout or transparent area whose size, e.g.length and/or width, corresponds with the deliverable volume of themedicament container, allows for applying medicament containers withdifferent deliverable volumes within the same shell of the drug deliverydevice without having to adapt the shell or selecting shells withdifferent window sizes for medicament containers with differentdeliverable volumes which requires different moulding tools. Adaptingthe label instead provides a much cheaper solution.

The medicament container may for example, be a syringe with a fixedinjection needle or cartridge having an end adapted to be connected to aremovable injection needle.

The shell may be a substantially tubular part.

In an exemplary embodiment, the label is selected such that the size ofthe cutout or transparent area corresponds to one of a plurality ofdifferent deliverable volumes of medicament within a respectivemedicament container, e.g. 0.3 ml, 0.5 ml and 1.0 ml. The smaller thevolume, the smaller the cutout or transparent area of the label can bemade.

In an exemplary embodiment, the foil is opaque except for the cutout ortransparent area in order to obscure interiors of the drug deliverydevice outside the deliverable volume. The external design of the drugdelivery device may thus be adapted for different products, e.g. bycolouring the opaque parts of the label and/or printing further relevantinformation thereon while the internals of the shell aside from the partof the medicament container holding the deliverable volume are hiddenfrom view.

In an exemplary embodiment, the cutout or transparent area is pointed toindicate a distal direction when applied to the shell of the drugdelivery device. The distal direction in the context of the presentdisclosure is the direction of an end of the drug delivery device, whichis intended to be closest to an injection site, e.g. a patient's skin,during delivery of the medicament. Giving the cutout or transparent areaa pointed appearance allows the user to easily identify which end of thedrug delivery device has to be placed against the injection site.

In an exemplary embodiment, at least one arrow is printed on the firstsurface to indicate a distal direction when applied to the shell of thedrug delivery device. The arrow allows the user to easily identify whichend of the drug delivery device has to be placed against the injectionsite. In an exemplary embodiment, the arrow is printed between twocutouts or transparent areas.

In an exemplary embodiment a line grid and/or a scale is printed on thefoil adjacent the cutout or transparent area. This allows the user todetermine the progress of the drug delivery, e.g. by observing aposition of a stopper within the medicament container with respect tothe line grid or scale.

In an exemplary embodiment, the second surface is coated with anadhesive.

In an exemplary embodiment, an outer surface of the shell is coated withan adhesive. This allows applying a non-adhesive label.

The shell only has to be transparent in an area adapted to contain themedicament container, in particular the one with the greatestdeliverable volume. In another exemplary embodiment, the entire shellmay be transparent.

According to an aspect of the present disclosure a kit for assembling adrug delivery device is provided. the kit comprises:

-   -   a shell adapted to contain one of a plurality of medicament        containers prefilled with different deliverable volumes of a        medicament, wherein the shell is transparent at least in an area        adapted to contain the medicament container, and    -   a plurality of labels adapted to be arranged on the shell,        wherein each one of the plurality of labels comprises a foil        having a first surface and a second surface which is adapted to        be connected to the shell, wherein at least one cutout or        transparent area is arranged in the foil of each one of the        plurality of labels, the at least one cutout or transparent area        being adapted to be placed on the shell such that a medicament        container arrangeable or arranged within the shell is visible        through the cutout or transparent area, wherein the plurality of        labels comprises different labels differing in a size of their        respective at least one cutout or transparent area to allow        inspection of the deliverable volumes of different medicament        containers out of the plurality of medicament containers.

Selecting a label with a cutout or transparent area whose size, e.g.length and/or width, corresponds with the deliverable volume of themedicament container allows for applying medicament containers withdifferent deliverable volumes within the same shell of the drug deliverydevice without having to adapt the shell. Adapting the label insteadprovides a much cheaper solution.

According to another aspect of the present disclosure, a method ofassembling a drug delivery device comprises:

-   -   providing a shell which is transparent at least in an area        adapted to contain one of a plurality of medicament containers        prefilled with different deliverable volumes of a medicament,        -   selecting a medicament container out of the plurality of            medicament containers to be inserted in the shell and            prefilled with a defined deliverable volume of a medicament,        -   selecting a label out of a plurality of labels, each one            having at least one cutout or transparent area exhibiting a            size adapted to allow inspection of the deliverable volume            of medicament within at least one out of plurality of            medicament containers, wherein the label is selected such            that the size of its at least one cutout or transparent area            corresponds to the selected medicament container, and        -   applying the label onto the shell to allow inspection of the            deliverable volume of the medicament within the selected            medicament container through the at least one cutout or            transparent area.

In an exemplary embodiment, the cutout or transparent area is pointed,wherein the label is applied to the shell such that the pointed cutoutor transparent area indicates a distal direction.

In an exemplary embodiment, at least one arrow is printed on the firstsurface, wherein the label is applied to the shell such that the arrowindicates a distal direction.

Selecting a label with a cutout or transparent area whose size, e.g.length and/or width, corresponds with the deliverable volume of themedicament container allows for applying medicament containers withdifferent deliverable volumes within the same shell of the drug deliverydevice without having to adapt the shell. Adapting the label insteadprovides a much cheaper solution. The shell only has to be transparentin an area adapted to contain the medicament container, in particularthe one with the greatest deliverable volume. In another exemplaryembodiment, the entire shell may be transparent.

According to yet another aspect of the present disclosure, a label for adrug delivery device is provided, the label comprising a foil having afirst surface and a second surface which is adapted to be adhesivelyconnected to a shell of the drug delivery device, wherein at least onecutout or transparent area is arranged in the foil adapted to be placedon the shell such that a medicament container arranged within the shellis visible through the cutout or transparent area, wherein a size of thecutout or transparent area is selected to allow inspection of thedeliverable volume of medicament within the medicament container whenthe label is applied to the shell.

Further scope of applicability of the present disclosure will becomeapparent from the detailed description given hereinafter. However, itshould be understood that the detailed description and specificexamples, while indicating exemplary embodiments of the disclosure, aregiven by way of illustration only, since various changes andmodifications within the spirit and scope of the disclosure will becomeapparent to those skilled in the art from this detailed description.

BRIEF DESCRIPTION OF THE FIGURES

The present disclosure will become more fully understood from thedetailed description given below and the accompanying drawings, whichare given by way of illustration only, and do not limit the presentdisclosure, and wherein:

FIG. 1 is a schematic view of a medicament container adapted to hold afirst deliverable volume of a medicament,

FIG. 2 is a schematic view of a medicament container adapted to hold asecond deliverable volume of a medicament,

FIG. 3 is a schematic view of a medicament container adapted to hold athird deliverable volume of a medicament,

FIG. 4 is a schematic view of a drug delivery device comprising a shelland a label with a cutout for allowing visual inspection of the firstdeliverable volume of the medicament within the medicament container ofFIG. 1 arranged within the shell,

FIG. 5 is a schematic view of a drug delivery device comprising a shelland a label with a cutout for allowing visual inspection of the seconddeliverable volume of the medicament within the medicament container ofFIG. 2 arranged within the shell,

FIG. 6 is a schematic view of a drug delivery device comprising a shelland a label with a cutout for allowing visual inspection of the thirddeliverable volume of the medicament within the medicament container ofFIG. 3 arranged within the shell,

FIG. 7 is a schematic view of a drug delivery device comprising a shelland a label with a cutout for allowing visual inspection of the thirddeliverable volume of the medicament within the medicament container ofFIG. 3 arranged within the shell, wherein the cutout is pointed toindicate a distal direction,

FIG. 8 is a schematic view of the label shown in FIG. 4 with anadditional arrow printed on the label to indicate the distal direction,

FIG. 9 is a schematic view of the label shown in FIG. 5 with anadditional line grid printed on the label,

FIG. 10 is a schematic view of the label shown in FIG. 6 ,

FIG. 11 is a schematic view of the label shown in FIG. 7 .

Corresponding parts are marked with the same reference symbols in allfigures.

DETAILED DESCRIPTION

FIG. 1 is a schematic view of a medicament container 1 adapted to hold afirst deliverable volume V1 of a medicament. The medicament container 1may comprise a barrel 2 defining a substantially cylindrical cavitywithin for receiving the first deliverable volume V1 of a medicament. Adistal end of the barrel 2 is closed and an injection needle 3 isarranged within the distal end to allow injection of the medicamentthrough the injection needle 3. In other, non-illustrated embodiments,the distal end of the barrel 2 does not have a fixed injection needle 3but may be adapted to releasably mount a removable injection needle. Astopper 4 is arranged within the barrel 2 to seal it proximally and toallow displacing the medicament when the stopper 4 is moved in a distaldirection D. The internal diameter of the barrel 2 and an initialposition of the stopper 4 define the first deliverable volume V1. In anexemplary embodiment, the first deliverable volume may be 0.3 ml.

FIG. 2 is a schematic view of a medicament container 1′ adapted to holda second deliverable volume V2 of a medicament. The medicament container1′ may be identical with the medicament container 1 of FIG. 1 . However,the initial position of the stopper 4 is more proximal than in FIG. 1 sothat the second deliverable volume V2 is greater than the firstdeliverable volume V1. In an exemplary embodiment, the seconddeliverable volume may be 0.5 ml.

FIG. 3 is a schematic view of a medicament container 1″ adapted to holda third deliverable volume V3 of a medicament. The medicament container1″ may be identical with the medicament containers 1, 1′ of FIGS. 1 and2 . However, the initial position of the stopper 4 is more proximal thanin FIG. 2 so that the third deliverable volume V3 is greater than thesecond deliverable volume V2. In an exemplary embodiment, the thirddeliverable volume may be 1.0 ml.

The skilled person will readily understand that medicament containers 1,1′, 1″ with other deliverable volumes may be provided.

FIG. 4 is a schematic view of a drug delivery device 5 comprising ashell 6 and a label 7 with a cutout 8 or transparent area for allowingvisual inspection of the first deliverable volume V1 of the medicamentwithin the medicament container 1 of FIG. 1 arranged within the shell 6.

The shell 6 may be adapted to contain one of a plurality of medicamentcontainers 1, 1′, 1″ prefilled with different deliverable volumes V1,V2, V3 of medicament, wherein the shell 6 is transparent at least in anarea adapted to contain the medicament container 1, 1′ 1″.

The label 7 comprises a foil having a first surface and a second surfacewhich is adapted to be adhesively connected to the shell 6. At least onecutout 8 or transparent area is arranged in the foil adapted to beplaced on the shell 6 such that the first deliverable volume V1 of themedicament container 1 arranged within the shell 6 is visible throughthe cutout 8 or transparent area. A size of the cutout 8 or transparentarea is selected to allow inspection of the first deliverable volume V1of medicament within the medicament container 1 when the label 7 isapplied to the shell 6 of the drug delivery device 5.

The label 7 is selected depending on the first deliverable volume V1 andadhesively arranged on the shell 6 to allow inspection of the firstdeliverable volume V1 of medicament within the medicament container 1.

This allows for applying medicament containers 1, 1′, 1″ with differentdeliverable volumes V1, V2, V3 within the same shell 6 of the drugdelivery device 5 without having to adapt the shell 6. Adapting thelabel 7 instead provides a much cheaper solution. The shell 6 only hasto be transparent in the area adapted to contain the medicamentcontainer 1, 1′, 1″. In particular, this transparent area is greatenough to allow inspection of the medicament container 1″ with thegreatest deliverable volume V3. In another exemplary embodiment, theentire shell 6 may be transparent.

In an exemplary embodiment, the label 7 or foil is opaque except for thecutout 8 or transparent area. The external design of the drug deliverydevice 5 may thus be adapted for different products, e.g. by colouringthe opaque parts of the label 7 and/or printing further relevantinformation on the first surface while the internals of the shell 6aside from the part of the medicament container 1 holding the firstdeliverable volume V1 are hidden from view.

In an exemplary embodiment, the second surface of the label 7 or foil iscoated with an adhesive in order to allow gluing the label 7 to theshell 6.

In another exemplary embodiment, an outer surface of the shell 6 iscoated with an adhesive. This allows applying a non-adhesive label 7onto the shell.

FIG. 5 is a schematic view of a drug delivery device 5 comprising ashell 6 and a label 7 with a cutout 8 for allowing visual inspection ofthe second deliverable volume V2 of the medicament within the medicamentcontainer 1′ of FIG. 2 arranged within the shell 6.

The drug delivery device 5 may be identical with the drug deliverydevice 5 of FIG. 4 . In particular, the same shell 6 may be used. Theonly difference is the label 7, which has a greater cutout 8 ortransparent area in order to allow inspection of the greater seconddeliverable volume V2.

FIG. 6 is a schematic view of a drug delivery device 5 comprising ashell 6 and a label 7 with a cutout 8 for allowing visual inspection ofthe third deliverable volume V3 of the medicament within the medicamentcontainer 1″ of FIG. 3 arranged within the shell 6.

The drug delivery device 5 may be identical with the drug deliverydevices 5 of FIGS. 4 and 5 . In particular, the same shell 6 may beused. The only difference is the label 7, which has an even greatercutout 8 or transparent area in order to allow inspection of the greaterthird deliverable volume V3.

FIG. 7 is a schematic view of a drug delivery device 5 comprising ashell 6 and a label 7 with a cutout 8 for allowing visual inspection ofthe third deliverable volume V3 of the medicament within the medicamentcontainer 1″ of FIG. 3 arranged within the shell 6

The drug delivery device 5 may be identical with the drug deliverydevices 5 of FIGS. 4 to 6 . In particular, the same shell 6 may be used.The only difference is the label 7, which has a cutout 8 or transparentarea sized to allow inspection of the third deliverable volume V3 as inFIG. 6 and which additionally has a pointed end 9 to indicate a distaldirection D.

FIG. 8 is a schematic view of the label 7 shown in FIG. 4 with anadditional arrow 10 printed on the first surface of the label 7 toindicate the distal direction D. In the illustrated embodiment, thelabel 7 comprises two cutouts 8 such that the first deliverable volumeV1 can be inspected from two sides when the label 7 is wrapped aroundthe shell 6. In the illustrated embodiment, the arrow 10 is printedbetween two cutouts 8 or transparent areas. The skilled person willunderstand that the arrow 10 may be printed on a different part of thelabel 7.

FIG. 9 is a schematic view of the label 7 shown in FIG. 5 with anadditional line grid 11 printed on the label 7 adjacent the cutout 8 ortransparent area.

FIG. 10 is a schematic view of the label shown in FIG. 6 .

FIG. 11 is a schematic view of the label shown in FIG. 7 .

The terms “drug” or “medicament” are used herein to describe one or morepharmaceutically active compounds. As described below, a drug ormedicament can include at least one small or large molecule, orcombinations thereof, in various types of formulations, for thetreatment of one or more diseases. Exemplary pharmaceutically activecompounds may include small molecules; polypeptides, peptides andproteins (e.g., hormones, growth factors, antibodies, antibodyfragments, and enzymes); carbohydrates and polysaccharides; and nucleicacids, double or single stranded DNA (including naked and cDNA), RNA,antisense nucleic acids such as antisense DNA and RNA, small interferingRNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleic acids maybe incorporated into molecular delivery systems such as vectors,plasmids, or liposomes. Mixtures of one or more of these drugs are alsocontemplated.

The term “drug delivery device” shall encompass any type of device orsystem configured to dispense a drug into a human or animal body.Without limitation, a drug delivery device may be an injection device(e.g., syringe, pen injector, auto injector, large-volume device, pump,perfusion system, or other device configured for intraocular,subcutaneous, intramuscular, or intravascular delivery), skin patch(e.g., osmotic, chemical, micro-needle), inhaler (e.g., nasal orpulmonary), implantable (e.g., coated stent, capsule), or feedingsystems for the gastro-intestinal tract. The presently described drugsmay be particularly useful with injection devices that include a needle,e.g., a small gauge needle.

The drug or medicament may be contained in a primary package or “drugcontainer” adapted for use with a drug delivery device. The drugcontainer may be, e.g., a cartridge, syringe, reservoir, or other vesselconfigured to provide a suitable chamber for storage (e.g., short- orlong-term storage) of one or more pharmaceutically active compounds. Forexample, in some instances, the chamber may be designed to store a drugfor at least one day (e.g., 1 to at least 30 days). In some instances,the chamber may be designed to store a drug for about 1 month to about 2years. Storage may occur at room temperature (e.g., about 20° C.), orrefrigerated temperatures (e.g., from about −4° C. to about 4° C.). Insome instances, the drug container may be or may include a dual-chambercartridge configured to store two or more components of a drugformulation (e.g., a drug and a diluent, or two different types ofdrugs) separately, one in each chamber. In such instances, the twochambers of the dual-chamber cartridge may be configured to allow mixingbetween the two or more components of the drug or medicament prior toand/or during dispensing into the human or animal body. For example, thetwo chambers may be configured such that they are in fluid communicationwith each other (e.g., by way of a conduit between the two chambers) andallow mixing of the two components when desired by a user prior todispensing. Alternatively or in addition, the two chambers may beconfigured to allow mixing as the components are being dispensed intothe human or animal body.

The drug delivery devices and drugs described herein can be used for thetreatment and/or prophylaxis of many different types of disorders.Exemplary disorders include, e.g., diabetes mellitus or complicationsassociated with diabetes mellitus such as diabetic retinopathy,thromboembolism disorders such as deep vein or pulmonarythromboembolism. Further exemplary disorders are acute coronary syndrome(ACS), angina, myocardial infarction, cancer, macular degeneration,inflammation, hay fever, atherosclerosis and/or rheumatoid arthritis.

Exemplary drugs for the treatment and/or prophylaxis of diabetesmellitus or complications associated with diabetes mellitus include aninsulin, e.g., human insulin, or a human insulin analogue or derivative,a glucagon-like peptide (GLP-1), GLP-1 analogues or GLP-1 receptoragonists, or an analogue or derivative thereof, a dipeptidyl peptidase-4(DPP4) inhibitor, or a pharmaceutically acceptable salt or solvatethereof, or any mixture thereof. As used herein, the term “derivative”refers to any substance, which is sufficiently structurally similar tothe original substance so as to have substantially similar functionalityor activity (e.g., therapeutic effectiveness).

Exemplary insulin analogues are Gly(A21), Arg(B31), Arg(B32) humaninsulin (insulin glargine); Lys(B3), Glu(B29) human insulin; Lys(B28),Pro(B29) human insulin; Asp(B28) human insulin; human insulin, whereinproline in position B28 is replaced by Asp, Lys, Leu, Val or Ala andwherein in position B29 Lys may be replaced by Pro; Ala(B26) humaninsulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30)human insulin.

Exemplary insulin derivatives are, for example, B29-N-myristoyl-des(B30)human insulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoylhuman insulin; B29-N-palmitoyl human insulin; B28-N-myristoylLysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin;B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30human insulin; B29-N—(N-palmitoyl-gamma-glutamyl)-des(B30) humaninsulin; B29-N—(N-lithocholyl-gamma-glutamyl)-des(B30) human insulin;B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin andB29-N-(ω-carboxyheptadecanoyl) human insulin. Exemplary GLP-1, GLP-1analogues and GLP-1 receptor agonists are, for example:Lixisenatide/AVE0010/ZP10/Lyxumia,Exenatide/Exendin-4/Byetta/Bydureon/ITCA 650/AC-2993 (a 39 amino acidpeptide which is produced by the salivary glands of the Gila monster),Liraglutide/Victoza, Semaglutide, Taspoglutide, Syncria/Albiglutide,Dulaglutide, rExendin-4, CJC-1134-PC, PB-1023, TTP-054,Langlenatide/HM-11260C, CM-3, GLP-1 Eligen, ORMD-0901, NN-9924, NN-9926,NN-9927, Nodexen, Viador-GLP-1, CVX-096, ZYOG-1, ZYD-1, GSK-2374697,DA-3091, MAR-701, MAR709, ZP-2929, ZP-3022, TT-401, BHM-034. MOD-6030,CAM-2036, DA-15864, ARI-2651, ARI-2255, Exenatide-XTEN andGlucagon-Xten.

An exemplary oligonucleotide is, for example: mipomersen/Kynamro, acholesterol-reducing antisense therapeutic for the treatment of familialhypercholesterolemia.

Exemplary DPP4 inhibitors are Vildagliptin, Sitagliptin, Denagliptin,Saxagliptin, Berberine.

Exemplary hormones include hypophysis hormones or hypothalamus hormonesor regulatory active peptides and their antagonists, such asGonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin),Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin,Triptorelin, Leuprorelin, Buserelin, Nafarelin, and Goserelin.

Exemplary polysaccharides include a glucosaminoglycane, a hyaluronicacid, a heparin, a low molecular weight heparin or an ultra-lowmolecular weight heparin or a derivative thereof, or a sulphatedpolysaccharide, e.g. a poly-sulphated form of the above-mentionedpolysaccharides, and/or a pharmaceutically acceptable salt thereof. Anexample of a pharmaceutically acceptable salt of a poly-sulphated lowmolecular weight heparin is enoxaparin sodium. An example of ahyaluronic acid derivative is Hylan G-F 20/Synvisc, a sodiumhyaluronate.

The term “antibody”, as used herein, refers to an immunoglobulinmolecule or an antigen-binding portion thereof. Examples ofantigen-binding portions of immunoglobulin molecules include F(ab) andF(ab′)₂ fragments, which retain the ability to bind antigen. Theantibody can be polyclonal, monoclonal, recombinant, chimeric,de-immunized or humanized, fully human, non-human, (e.g., murine), orsingle chain antibody. In some embodiments, the antibody has effectorfunction and can fix complement. In some embodiments, the antibody hasreduced or no ability to bind an Fc receptor. For example, the antibodycan be an isotype or subtype, an antibody fragment or mutant, which doesnot support binding to an Fc receptor, e.g., it has a mutagenized ordeleted Fc receptor binding region.

The terms “fragment” or “antibody fragment” refer to a polypeptidederived from an antibody polypeptide molecule (e.g., an antibody heavyand/or light chain polypeptide) that does not comprise a full-lengthantibody polypeptide, but that still comprises at least a portion of afull-length antibody polypeptide that is capable of binding to anantigen. Antibody fragments can comprise a cleaved portion of a fulllength antibody polypeptide, although the term is not limited to suchcleaved fragments. Antibody fragments that are useful in the presentdisclosure include, for example, Fab fragments, F(ab′)₂ fragments, scFv(single-chain Fv) fragments, linear antibodies, monospecific ormultispecific antibody fragments such as bispecific, trispecific, andmultispecific antibodies (e.g., diabodies, triabodies, tetrabodies),minibodies, chelating recombinant antibodies, tribodies or bibodies,intrabodies, nanobodies, small modular immunopharmaceuticals (SMIP),binding-domain immunoglobulin fusion proteins, camelized antibodies, andVHH containing antibodies. Additional examples of antigen-bindingantibody fragments are known in the art.

The terms “Complementarity-determining region” or “CDR” refer to shortpolypeptide sequences within the variable region of both heavy and lightchain polypeptides that are primarily responsible for mediating specificantigen recognition. The term “framework region” refers to amino acidsequences within the variable region of both heavy and light chainpolypeptides that are not CDR sequences, and are primarily responsiblefor maintaining correct positioning of the CDR sequences to permitantigen binding. Although the framework regions themselves typically donot directly participate in antigen binding, as is known in the art,certain residues within the framework regions of certain antibodies candirectly participate in antigen binding or can affect the ability of oneor more amino acids in CDRs to interact with antigen.

Exemplary antibodies are anti PCSK-9 mAb (e.g., Alirocumab), anti IL-6mAb (e.g., Sarilumab), and anti IL-4 mAb (e.g., Dupilumab).

The compounds described herein may be used in pharmaceuticalformulations comprising (a) the compound(s) or pharmaceuticallyacceptable salts thereof, and (b) a pharmaceutically acceptable carrier.The compounds may also be used in pharmaceutical formulations thatinclude one or more other active pharmaceutical ingredients or inpharmaceutical formulations in which the present compound or apharmaceutically acceptable salt thereof is the only active ingredient.Accordingly, the pharmaceutical formulations of the present disclosureencompass any formulation made by admixing a compound described hereinand a pharmaceutically acceptable carrier.

Pharmaceutically acceptable salts of any drug described herein are alsocontemplated for use in drug delivery devices. Pharmaceuticallyacceptable salts are for example acid addition salts and basic salts.Acid addition salts are e.g. HCl or HBr salts. Basic salts are e.g.salts having a cation selected from an alkali or alkaline earth metal,e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), whereinR1 to R4 independently of each other mean: hydrogen, an optionallysubstituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenylgroup, an optionally substituted C6-C10-aryl group, or an optionallysubstituted C6-C10-heteroaryl group. Further examples ofpharmaceutically acceptable salts are known to those of skill in thearts.

Pharmaceutically acceptable solvates are for example hydrates oralkanolates such as methanolates or ethanolates.

Those of skill in the art will understand that modifications (additionsand/or removals) of various components of the substances, formulations,apparatuses, methods, systems and embodiments described herein may bemade without departing from the full scope and spirit of the presentdisclosure, which encompass such modifications and any and allequivalents thereof.

LIST OF REFERENCES

-   -   1 medicament container    -   1′ medicament container    -   1″ medicament container    -   2 barrel    -   3 injection needle    -   4 stopper    -   5 drug delivery device    -   6 shell    -   7 label    -   8 cutout    -   9 pointed end    -   10 arrow    -   11 line grid    -   D distal direction    -   V1 first deliverable volume    -   V2 second deliverable volume    -   V3 third deliverable volume

1-14. (canceled)
 15. A method of assembling a drug delivery device, themethod comprising: selecting a medicament container to be inserted in ashell; selecting a label out of a plurality of labels, each one havingat least one cutout or transparent area sized to allow inspection of adeliverable volume of medicament within the medicament container,wherein the label is selected such that a size of the at least onecutout or transparent area corresponds to a selected medicamentcontainer; and applying the label onto the shell to allow inspection ofa deliverable volume of medicament within the selected medicamentcontainer through the at least one cutout or transparent area.
 16. Themethod according to claim 15, wherein applying the label comprisesapplying the label to the shell such that a pointed cutout ortransparent area indicates a distal direction.
 17. The method accordingto claim 15, wherein applying the label comprises applying the label tothe shell such that an arrow indicates a distal direction, wherein thearrow is printed on a first surface of the label.
 18. The methodaccording to claim 17, wherein applying the label comprises applying thelabel to the shell such that the arrow indicates the distal direction,wherein the arrow is printed between two cutouts or transparent areas.19. The method of claim 17, wherein selecting the label comprisesselecting the label comprising a foil having a first surface and asecond surface, wherein the at least one cutout or transparent area isarranged in the foil.
 20. The method of claim 19, wherein selecting thelabel comprises selecting the label comprising a line grid and scaleprinted on the foil adjacent the cutout or transparent area.
 21. Themethod of claim 19, wherein applying the label comprises connecting anadhesive coating of the second surface of the foil to the shell.
 22. Themethod of claim 19, wherein applying the label comprises arranging anopaque part of the foil relative to the shell such that interiorportions of the drug delivery device outside a deliverable volume areobscured.
 23. The method of claim 22, comprising filling the medicamentcontainer with a first deliverable volume that is different from agreater deliverable volume, wherein the medicament container is adaptedto store the greater deliverable volume,
 24. The method of claim 23,wherein applying the label comprises covering a part of the medicamentcontainer that would be necessary to allow inspection of the greaterdelivery volume with a portion of the opaque part of the foil, whereinthe portion of the opaque part of the foil is arranged proximally of thecutout or of the transparent area.
 25. The method of claim 19, whereinapplying the label comprises connecting an adhesive coating of an outersurface of the shell to the foil.
 25. The method of claim 17, comprisingselecting a shell that is substantially transparent.